Compositions for inhibiting the scent tracking ability of mosquitoes in environmentally defined three dimensional spaces

ABSTRACT

Composition for inhibiting the ability of mosquitoes to locate a target by olfactory emissions of the target comprise a composition of at least one inhibiting compound selected from the group consisting of 3-methyl-1-alkene-3-ols of the formula: 
                         
and 3-methyl-1-alkyn-3-ols of the formula:
 
                         
wherein R 1  and R 2  are each independently a saturated or unsaturated aliphatic hydrocarbon group containing from 1 to about 12 carbon atoms, in a vehicle base that is a porous or waxy medium. The composition being capable of dispensing the inhibiting compound in an non-lethal amount effective to inhibit the ability of mosquitoes to sense a target in a three dimensional environmental space.

RELATED APPLICATIONS

This application is a continuation-in-part of application Ser. No.10/051,706, filed Jan. 17, 2002 now abandoned, which in turn was adivisional application of then application Ser. No. 09/307,907, filedMay 10, 1999, now U.S. Pat. No. 6,362,235 B1, the priorities of whichare claimed under 335 U.S.C. 120.

FIELD OF THE INVENTION

This invention relates to a method, apparatus and compositions forinhibiting the ability of mosquitoes to locate or track a human body byscent detection. More particularly, the invention relates to the use ofcertain compounds in compositions and apparatus to inhibit mosquitoes'ability to detect humans by scent detection.

BACKGROUND

Compounds, compositions and formulations for protecting human beingsfrom being bitten by mosquitoes are known in the art. Generally, thesecompounds, compositions and formulations are based on their ability topersist on the skin of the person upon topical or surface applicationfor a time sufficient to repel mosquitoes. Numerous adjuvant materialshave been added to mosquito repellents to increase the persistence ofthe repellents to the skin of a person. However, despite the variousattempts to improve the repelling activity of the known mosquitorepellents, these attempts have generally not been successful, as almostanyone who has used such mosquito repellents can attest.

Thus, the art has been searching for new and more effective repellentsagainst mosquitoes. However, the search for more effective mosquitorepellents has not generally been met with success since most mosquitorepellents have been found only to possess a limited degree ofrepellency and are generally not particularly effective. There is,therefore, a need for more effective means to deter mosquitoes from evenlocating and biting humans and other targets such as livestock.Moreover, this need has recently become more acute and urgent becausemosquitoes have been discovered to be carriers of significant diseasesthat can be passed on to a target by the mosquitoes biting the target. Afurther need is to be able to reduce the use of environmentallyunfriendly pesticides.

In U.S. Pat. No. 4,933,371 there is a disclosure of using stocksolutions of 2.5, 5 and 10 percent linalool in Tween 80 and water tokill mosquitoes. In contrast to this, the present invention does notwant to kill mosquitoes. Rather, in the present invention the object isto prevent mosquitoes from sensing a target, not to kill them.

SUMMARY OF THE INVENTION

The inventors have discovered that compounds, compositions andformulations heretofore proposed as repellents for mosquitoes havelacked the necessary efficacy due to the ability of mosquitoes to locateand be drawn to the targets by olfactory emissions of the target. Thus,if a mosquito enters a zone or space where a potential target islocated, the mosquito can be attracted to the target by olfactoryemissions of the target and, this olfactory attraction is sufficient toovercome any repellency activity of the repellent compound, compositionor formulation applied on the target. Therefore, the present inventionprovides compositions and formulations containing compounds usable inmethods and apparatus for inhibiting the olfactory target trackingabilities of mosquitoes when an effective amount of the inhibitingcompound(s) is/are dispersed in a three dimensional atmospheric space.

According to this invention, the ability of mosquitoes to locate atarget is inhibited by dispensing into a spatial area a non-lethalinhibiting effective amount of at least one inhibiting compound selectedfrom the group consisting of 3-methyl-1-alkene-3-ols of the formula:

and 3-methyl-1-alkyn-3-ols of the formula:

wherein R¹ and R² are each independently a saturated or unsaturatedaliphatic hydrocarbon group containing from 1 to about 12 carbon atoms.

The inhibiting compound can be dispensed into the three dimensionalatmospheric space by any suitable means sufficient to provide aninhibiting effective amount of the inhibiting compound(s). Suchdispensing means includes, for example, evaporation, atomization andionic dispersion of the inhibiting compound from any suitablecomposition or formulation. Such composition or formulation willgenerally comprise a base vehicle containing at least one of theinhibiting compounds.

DETAILED SUMMARY OF THE INVENTION

The inventors have discovered that if a non-lethal effective amount ofat least one inhibiting compound selected from the group consisting of3-methyl-1-alkene-3-ols of the formula:

and 3-methyl-1-alkyn-3-ols of the formula:

wherein R¹ and R² are each independently a saturated or unsaturatedaliphatic hydrocarbon group containing from 1 to about 12 carbon atomsis dispensed into the atmosphere of a three dimensional environmentalspace, the ability of mosquitoes to locate and track a target, such ashumans or livestock, by the target's olfactory emissions is inhibited.

Any suitable 3-methyl-1-alkene-3-ols or 3-methyl-1-alkyn-3-ol of theformulas may be employed in the method, compositions and apparatus ofthis invention. Especially suitable inhibiting compounds are nerolidol,3-methyl-1-octen-3-ol, linalool and dehydrolinalool. Depending on theparticular mosquito species, either the 3-methyl-1-alkyn-3-ols or the3-methyl-1-alkene-3-ols are better inhibitors than the other class ofcomponents and will be preferred for that species of mosquito. Theinhibiting compounds may be utilized singly or as mixtures of two ormore of such compounds.

Any suitable non-lethal inhibiting effective amount of the inhibitingcompound(s) may be employed. By “non-lethal” amounts is meant that theamount of inhibiting compounds releasable from the composition into theenvironmental area is insufficient to kill mosquitoes. Such inhibitingeffective amounts can include amounts, based on the square footage ofland or base surface area of the environmental area to be treated,preferably within the range of from about 0.000005 g/hr/ft² to about0.004 g/hr/ft², more preferably amounts within the range of from about0.00015 g/hr/ft² to about 0.0002 g/hr/ft², and especially an amount ofabout 0.00016 g/hr/ft².

The inhibiting compounds for use in this invention may be provided in anessentially pure form of the inhibiting compounds or as a component of anatural essential oil having a concentration of an inhibiting compoundsufficient to make it practical and feasible to dispense an inhibitingeffective amount of inhibiting compound. Generally, the essential oilwill contain a concentration of the inhibiting compound of at leastabout 2%, preferably at least about 5%, and especially at least about50% by weight. For example, the inhibiting compound can be provided as asynthetically produced, essentially pure compound or as a component ofan essential oil such as basil oil, ho wood oil and the like.

The inhibiting compounds of this invention, or essential oils containingsuch inhibiting compounds, may be employed in any suitable formulationsuitable for dispensing inhibiting effective amounts of the compounds.The compounds will generally be employed in formulations comprising asuitable vehicle containing the inhibiting compounds. For example, theinhibiting compound can be formulated in a specially formulated waxy orwax-like medium or vehicle engineered to release desired amounts ofvaporous inhibiting compound at ambient temperatures, such as thosemediums or vehicles available from Koster Keunen of Watertown, Conn., orfrom candles. An example of such a wax-like medium available from KosterKeunen is known as Insect Repellent Wax Bar No. 9, which is a blend ofwaxes having the following general composition: fatty acids ranging incarbon chain length of from C₁₆ to C₂₂, fatty alcohols ranging in carbonchain length of from C₁₆ to C₂₂, paraffinic hydrocarbons ranging incarbon chain length of from C₁₉ to C₄₇, branched hydrocarbons ranging incarbon chain length of from C₂₃ to C₆₉, beeswax and other natural waxessuch as candelilla and carnauba. The wax mixture will generally beformulated with concentrations of the inhibiting compounds of thisinvention ranging from about 20% to 60% and the formulation has acongealing point which may vary from about 75° C. to about 45° C.Alternatively, the inhibiting compound can be formulated in a porousmedium or vehicle suitable for releasing effective amounts of theinhibiting compound. As an example of such porous medium or vehicle is apolyester membrane material having micropores encasing a block ofinhibiting compound saturated fibers that gradually releases theinhibiting compound so that it permeates the microporous membrane and isreleased to the environment. Such porous membrane known as World ofFragrance™ cups is available from Waterbury Companies, Inc. ofWaterbury, Conn.

The formulations can be placed in any suitable container or device fordispensing the inhibiting compound. For example, the formulations can beplaced in a suitable fan-equipped device so that one can obtain, forexample, fan-driven evaporation of the inhibiting compound from a porousmedium or wax-like medium containing the inhibiting compound. Asexamples of such fan-equipped devices, there can be mentioned thedevices disclosed in U.S. Pat. No. 5,370,829 of Waterbury Companies,Inc. and the apparatus disclosed in U.S. Pat. No. 5,799,436 ofBiosensory Insect Control Corporation, each of said patents beingincorporated herein by reference thereto.

Another suitable means of dispensing the inhibiting compound is byatomization and/or ionic dispersion of the compound as suitable-sized,positively-charged droplets from a suitable atomization or ionicdispersing apparatus, such as the Ionic Wind™ device, available fromBrandenburg, Ltd. of Brierery Hill, United Kingdom.

The inhibiting compounds of this invention are effective againstmosquitoes, such as for example, Aedes taeniorhyncus (Black Salt Marshmosquito), Culex nigripalpus, Aedes aegypti, Aedes albpictus (AsianTiger mosquito), Culex pipiens (common house mosquito) and the like.

The use of this invention is illustrated by the following non-limitedexamples.

EXAMPLE 1

A triple cage, dual-port olfactometer, illustrated and described indetail by Posey et al. J. Med. Entomol. 35(3), 330-334 (1998), was usedto study the responses of 6 to 8 day old, laboratory-reared adult femaleAedes aegypti mosquitoes. This system allows mosquitoes to choosebetween two different stimuli. The olfactometer is constructed of clearacrylic, comprises three test chambers in a tiered configuration, haspaired removable sleeves, and mosquito traps on each chamber, and isequipped with a filtered external air supply system that allows precisetemperature (+/−0.5° C.) and relative humidity (+/−2%) control. Only onechamber at a time was used for the tests. Outside air was conditionedprior to entry through the choice ports, the mosquito trap, and theolfactometer by passing through a series of charcoal filters and thenheated and humidified, if necessary.

One hour before initiation of tests, about 75 female Ae. aegyptimosquitoes were aspirated into the olfactometer chamber and allowed toacclimatize for that one hour before testing. Test compounds were placedinto test ports upwind of the traps and olfactometer chamber. Acompletely randomized design was used for cage position.

Competitive tests were conducted. In these competitive tests, theinhibiting compound was placed into one of the ports (treatment port);the second port (check port) had the same apparatus but no chemicalinhibiting compound. In these tests, inhibiting compounds were presentedin glass Pyrex petri dishes (60×15 mm) that had been cleaned andsterilized in a vacuum oven and then handled only with gloves tominimize any chance of contamination and placed into one port (TreatmentPort) along with another petri dish containing 500 μL of Clara Sludge(CS), a synthetic human attractant. The other port (Check Port)contained an untreated petri with no inhibiting compound and a secondpetri dish containing 500 μL CS. Various concentrations (25, 100, 250,500 and 1000 μL) of the compounds were used in these tests. Each testwas conducted for a period of 3 minutes; the number of mosquitoestrapped in the baited ports, and those remaining in the cage, werecounted. The data are then presented as a percentage of total mosquitoesin the cage that were attracted to each port and the percentage ofmosquitoes remaining in the cage (i.e., not attracted to either port).

Results of the competitive tests are set forth in the following Table 1.

TABLE 1 Competitive Tests % Mosquitoes Entering Treatment Control Port %Mosquitoes Test Compound and Port (Inhib- (Human Scent Remaining inAmount itor Port) Port) Cage Dehydrolinalool 25 30.23 50.77 19 microliter Dehydrolinalool 100 31.13 53.87 15 micro liter Dehydrolinalool 25022.6 44.6 32.8 micro liter Dehydrolinalool 500 24.8 56.47 24.18 microliter Dehydrolinalool 1000 26.11 42.76 27.12 micro liter Linalool 25micro 21.98 56.89 21.14 liter Linalool 100 micro 31.3 45.61 23.08 literLinalool 250 micro 16.57 47.3 36.13 liter Linalool 500 micro 16.13 44.5639.31 liter Linalool 1000 micro 27.24 44.14 31.3 literFor comparison purposes, 500 μL of the human scent (CS) was also placedalone in the Treatment Port, and with only an empty petri dish in theCheck Port. The Treatment Port with the CS attracted 69 to 65% of themosquitoes, with 30 to 35% of the mosquitoes remaining in the cage, andnone being attracted to the Check Port with only the petri dish. At alltested concentration levels, linalool and dehydrolinalool are shown togreatly inhibit the ability of mosquitoes to locate the human scent (CS)as shown by the much lower percentage of mosquitoes captured in theTreatment Port compared to the Human Scent Port.

EXAMPLE 2

Tests identical to that described in Example 1 were conducted with testcompounds when employed together with the synthetic human attractant(CS) in a port. The test combinations were:

-   -   (1) CS vs. CS (comparison)    -   (2) dehydrolinalool+CS vs. CS    -   (3) linalool+CS vs. CS        Also for comparison purposes, a known topical mosquito        repellent, Deet, namely N,N-diethyl-3-methylbenzamide, was        employed to compare to linalool and to dehydrolinalool. Each        test compound was tested at 100, 250 and 500 μL. The results are        presented in Tables 2, 3 and 4. The results are again presented        as percent mosquitoes attracted to Ports 1 or 2 or not attracted        to either port.

TABLE 2 (100 micro liter treatments) % Mosquitoes % Mosquitoes EnteringRemaining in Test Compound and Amount Port 1 Port 2 Cage 1 Human scentvs. 2 human 50.5 44 5.5 scent 1 Dehydrolinalool vs. 2 18.1 63 18.9 humanscent 1 Linalool vs. 2 human scent 22.5 50.7 26.8 1 Deet vs. 2dehydrolinalool 60.1 20.1 19.8 1 Deet vs. 2 linalool 56.3 17.5 26.2

TABLE 3 (250 micro liter treatments) % Mosquitoes % Mosquitoes EnteringRemaining in Test Compound and Amount Port 1 Port 2 Cage 1 Human scentvs. 2 human 49.9 39.4 8.7 scent 1 Dehydrolinalool vs. 2 20.1 59.2 20.6human scent 1 Linalool vs. 2 human scent 14.9 56.8 28.4 1 Deet vs. 2dehydrolinalool 48.8 22.5 29.2 1 Deet vs. 2 linalool 48.1 25.7 26.2

TABLE 4 (500 micro liter treatments) % Mosquitoes % Mosquitoes EnteringRemaining in Test Compound and Amount Port 1 Port 2 Cage 1 Human scentvs. 2 human 47.3 46.8 5.9 scent 1 Dehydrolinalool vs. 2 20.6 55.5 23.9human scent 1 Linalool vs. 2 human scent 25.7 55.6 18.7 1 Deet vs. 2dehydrolinalool 42.1 30.3 27.6 1 Deet vs. 2 linalool 49.5 23.1 27.3

EXAMPLE 3

In a further test of the inhibiting ability of the compounds of thisinvention, the following field test was conducted using linalool as theinhibiting compound. The study was conducted on a site adjacent to awooded wetland breeding area in Sarasota, Fla. A trap baited with 200ml/min CO₂, equivalent to the respiration of a 91 kg (200 lb) man, rancontinuously each night as an experimental control. The trap collectionswere first used to count the mosquito population and were then examineto identify the species present. The mosquito population was about 91%Culex nigripalpus, the St. Louis encephalitis vector in Florida.

The experimental design was a 2×2 Latin Square. Tests were conducted intwo open areas 24 meters (80 feet) apart labeled Locations 1 and 2. Eacharea was 2.4 meters×2.4 meters (8 ft×8 ft), i.e., 5.76 m² (64 ft²).Wooden poles 1.38 meters (4.5 feet) high and having inhibiting compounddispensers thereon were driven into the ground at the corners of thesquare area. On alternate nights, one area was unprotected by inhibitingcompound while the other area had inhibiting compound dispensed from thedispenser. In operation, the dispenser emitted linalool inhibitor having95% active ingredient at a rate of 20 mg/hr to 40 mg/hr.

Landing counts were taken from the arms, legs and torso of a testsubject known to be moderately attractive to mosquitoes who was seatedin the center of the square area. At 15-minute intervals over a periodof 2 to 3 hours during peak mosquito activity, the subject changed hisposition, alternating between Locations 1 and 2. If there was noactivity for five minutes, the test subject walked around the insideperimeter of the square area in an attempt to draw attention to hispresence. Mosquitoes were killed to prevent double counting.

The mosquitoes were observed to exhibit a behavior similar to swarmingeach evening around 6:45 to 7:00 PM. On some cue, they emerge en massefrom the wooded wetland and fan out in a radial direction foraging forblood hosts. The period of peak activity is evidenced by a sharpincrease in landing counts followed by a sharp decrease as the wave ofoutbound mosquitoes passes the test location. This behavior introducestwo variables that must be taken into account. The first affects theexperimental design and the second affects the interpretation of theresults.

To be most accurate, an experimental trial must span a period before andafter peak activity. Ending a trial at or near the time of peakactivity, for example, will result in a larger landing count for thetreatment used last, skewing the result. The starting time and durationof trials were adjusted to avoid distorting the landing counts.

It is also recognized that the landing counts represent both:

-   -   1. mosquitoes drawn to the human subject by his scent, and    -   2. mosquitoes that encounter the human subject because he is in        their line of flight as they leave the water.        If the inhibitor impairs the mosquitoes' scent-tracking ability,        it will affect the former but not the latter. This fact must be        taken into account when interpreting the results.

The sites selected represent a worse case condition that is experiencedonly by those located adjacent to a breeding site and in the line offlight as the mosquitoes come off the water. For a measure ofperformance more typical of the average homeowner, a test was conductedfrom 7:00 AM to 9:00 AM in the morning when activity is not at its peak.

Linalool reduced the mosquito landing counts by an average of 53% overthe three trials. The unprotected human subject experienced 286 landingscompared to 135 landings when surrounded by linalool dispensed from thedispensers.

The range for individual trials is a reduction of landings by 36% to 68%during periods of peak activity and by 73% in the morning trial whenmosquito activity was light.

These results indicate linalool's ability to reduce the landing countsof Culex nigripalpus on humans in open areas by inhibiting themosquitoes' ability to track the human's olfactory emissions.

With the foregoing description of the invention, those skilled in theart will appreciate that modifications may be made to the inventionwithout departing from the spirit thereof. Therefore, it is not intendedthat the scope of the invention be limited to the specific embodimentsillustrated and described.

1. A composition for inhibiting the ability of mosquitoes to sense atarget within a three dimensional environmental space having a land orbase surface area, the composition comprising: (A) a non-lethalinhibiting effective amount of at least one inhibiting compound selectedfrom the group consisting of 3-methyl-1-alkene-3-ols of the formula:

and 3-methyl-1-alkyn-3-ols of the formula:

wherein R¹ and R² are each independently a saturated or unsaturatedaliphatic hydrocarbon group containing from 1 to about 12 carbon atoms,in (B) a base vehicle comprising a porous or waxy medium, wherein thenon-lethal inhibiting effective amount of the at least one inhibitingcompound is sufficient to inhibit the ability of mosquitoes to sense atarget in the three dimensional environmental space.
 2. The compositionaccording to claim 1, wherein the composition is sufficient to providein an atmosphere of the three dimensional environmental space anon-lethal inhibiting effective amount of the at least one inhibitingcompound ranging from about 0.000005 g/hr/ft² to about 0.0004 g/hr/ft²per square footage of the land or base surface area of the threedimensional environmental space.
 3. The composition according to claim1, wherein the composition is sufficient to provide in an atmosphere ofthe three dimensional environmental space a non-lethal inhibitingeffective amount of the at least one inhibiting compound ranging fromabout 0.00015 g/hr/ft² to about 0.0002 g/hr/ft² per square footage ofthe land or base surface area of the three dimensional environmentalspace.
 4. The composition according to claim 1, wherein the at least oneinhibiting compound is selected from nerolidol, 3-methyl-1-octen-3-ol,linalool and dehydrolinalool.
 5. The composition according to claim 1,wherein the at least one inhibiting compound comprises linalool.
 6. Thecomposition according to claim 1, wherein the at least one inhibitingcompound comprises dehydrolinalool.
 7. The composition according toclaim 1, wherein the composition is capable of dispensing the non-lethalamount of at least one inhibiting compound into an atmosphere of thethree dimensional environmental space by a method selected fromvolatilization, evaporation, atomization and ionic dispersion of the atleast one inhibiting compound.
 8. The composition according to claim 7,wherein the base vehicle is a porous medium and the composition iscapable of dispensing the at least one inhibiting compound by fan-drivenevaporation of the at least one inhibiting compound.
 9. The compositionaccording to claim 5, wherein the vehicle is a porous medium and thelinalool in the composition is capable of being dispensed from thecomposition by fan-driven evaporation of the linalool.
 10. Thecomposition according to claim 6, wherein vehicle is a porous medium andthe dehydrolinalool in the composition is capable of being dispensedfrom the composition by fan-driven evaporation of the dehydrolinalool.11. The composition according to claim 6, wherein the vehicle is a waxymedium and the dehydrolinalool in the composition is capable of beingdispensed from the composition by fan-driven evaporation of thedehydrolinalool.
 12. The composition according to claim 6, wherein thedehydrolinalool in the composition is capable of being dispersed fromthe composition by atomization of the dehydrolinalool.
 13. Thecomposition according to claim 6, wherein the dehydrolinalool in thecomposition is capable of being dispensed from the composition by ionicdispersion of the dehydrolinalool.
 14. A composition for inhibiting theability of mosquitoes to sense a target within a three dimensionalenvironmental space having a land or base surface area, the compositioncomprising: (A) a non-lethal inhibiting effective amount of at least oneinhibiting compound selected from the group consisting of 3-methyl1-alken-3-ols of the formula:

and 3-methyl-1-alkyn-3-ols of the formula:

wherein R¹ and R² are each independently a saturated or unsaturatedaliphatic hydrocarbon group containing from 1 to 12 carbon atoms, in (B)a base vehicle that is a waxy medium, wherein the non-lethal inhibitingeffective amount of the at least one inhibiting compound is sufficientto inhibit the ability of mosquitoes to sense a target in the threedimensional environmental space.
 15. A composition of claim 14 whereinthe at least one inhibiting compound is linalool.
 16. A composition ofclaim 14 wherein the at least one inhibiting compound isdehydrolinalool.
 17. A composition for inhibiting the ability ofmosquitoes to sense a target within a three dimensional environmentalspace having a land or base surface area, the composition consistingessentially of: (A) a non-lethal inhibiting effective amount of at leastone inhibiting compound selected from the group consisting of3-methyl-1-alken-3-ols of the formula:

and 3-methyl-1-alkyn-3-ols of the formula:

wherein R¹ and R² are each independently a saturated or unsaturatedaliphatic hydrocarbon group containing from 1 to about 12 carbon atoms,in (B) a base vehicle that is a waxy medium, wherein the non-lethalinhibiting effective amount of the at least one inhibiting compound issufficient to inhibit the ability of mosquitoes to sense a target in thethree dimensional environmental space.
 18. A composition according toclaim 14 or claim 17 wherein the composition is capable of dispensing,by a method selected from the group consisting of atomization, ionicdispersion, and fan-driven evaporation, the at least one inhibitingcompound in a non-lethal amount from the composition into an atmosphereof a three dimensional space sufficient to provide a non-lethalinhibiting effective amount of the at least one inhibiting compoundsufficient to inhibit the ability of mosquitoes to sense a target in athree dimensional environmental space.
 19. A composition according toclaim 18 wherein the at least one inhibiting compound is linalool.
 20. Acomposition according to claim 1 wherein the inhibiting compound isprovided as a synthetically produced, essentially pure compound.